The objective of this program is to analyze problems related to neoplasia using the fruit fly Drosophila. Although this is a rather unconventional organism in cancer research, the abundance of genetic variation and the availability of methods for genetic manipulation make possible a number of unusual approaches to the cancer problem. In one series of experiments we are analyzing genetically induced neoplasia by the isolation and use of temperature-sensitive mutations causing neoplastic changes. Such mutations may make it possible to control the onset and reversion of neoplasia, so that these transitions can be studied in detail. We are also using genetic mosaics and surgical methods to study the interactions between normal and neoplastic cells. A second goal is to examine the way in which exogenous DNA might interact with nuclear DNA. Our approach is to surgically inject purified DNA or DNA fractions from adult flies of one genotype into Drosophila embryos of another genotype and to analyze the interaction of the foreign and host DNA by genetic means. We have already shown that DNA which is injected into young Drosophila embryos can produce heritable genetic alterations in the resulting flies. Our third objective is to study the regulation of the cell cycle in both normal and cancerous cells by the use of temperature-sensitive mutations which block progress through the cycle. Such mutations could be used to study the interdependence of various steps in the cell cycle.